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The purpose of this study was to investigate the relationship between sodium nitroprusside-induced relaxation, inhibition of the sodium-potassium pump, and cyclic guanosine monophosphate. Exposure of rat thoracic aorta to ouabain, or potassium- or magnesium-free Krebs-Ringer bicarbonate solution, procedures which presumably inhibit the sodium-potassium pump, or to potassium chloride or tetraethylammonium, membrane-depolarizing agents, inhibited relaxation to nitroprusside. These conditions had little or no effect on the elevated cyclic guanosine monophosphate levels at a concentration of nitroprusside (0.1 microM) that relaxed norepinephrine contracted tissues by 80%. However, at a maximum relaxant concentration of nitroprusside (1.0 microM), these conditions decreased the elevation of cyclic guanosine monophosphate. The inhibition of elevated cyclic guanosine monophosphate levels was independent of the endothelium, extracellular calcium, and the cyclic guanosine monophosphate phosphodiesterase inhibitor, M&B 22,948. The inhibitory effects of ouabain and of potassium- and magnesium-free solution on the increased levels of cyclic guanosine monophosphate caused by 1.0 microM nitroprusside were abolished when tissues were incubated without norepinephrine, or with norepinephrine in the presence of the alpha-adrenergic blocker, phentolamine. In contrast, a beta-adrenergic blocker, propranolol, had no effect on the ouabain-induced inhibition of elevated cyclic guanosine monophosphate levels, with norepinephrine present. These results are consistent with the hypothesis that membrane events regulate cyclic guanosine monophosphate synthesis. At nitroprusside concentrations greater than 0.1 microM, the formation of cyclic guanosine monophosphate appears to be coupled to the status of the smooth muscle cell membrane and integrity of the sodium-potassium pump.(ABSTRACT TRUNCATED AT 250 WORDS)
R M Rapoport, and
K Schwartz, and
F Murad
January 2010,
Journal of pharmacological sciences,
R M Rapoport, and
K Schwartz, and
F Murad
September 1991,
The Journal of pharmacology and experimental therapeutics,
R M Rapoport, and
K Schwartz, and
F Murad
February 1972,
European journal of pharmacology,
R M Rapoport, and
K Schwartz, and
F Murad
November 1997,
The Journal of pharmacology and experimental therapeutics,
R M Rapoport, and
K Schwartz, and
F Murad
January 1983,
Blood vessels,
R M Rapoport, and
K Schwartz, and
F Murad
January 1988,
General pharmacology,
R M Rapoport, and
K Schwartz, and
F Murad
January 1993,
Biochemistry and molecular biology international,
R M Rapoport, and
K Schwartz, and
F Murad
May 1989,
Neuroscience letters,
R M Rapoport, and
K Schwartz, and
F Murad
June 1982,
Archives internationales de pharmacodynamie et de therapie,
R M Rapoport, and
K Schwartz, and
F Murad
April 1989,
Proceedings of the National Science Council, Republic of China. Part B, Life sciences,
